Immunogenicity up to age 5 years following a single-dose or two-dose infant primary series of 10-valent or 13-valent pneumococcal conjugate vaccine each followed by a booster dose in South Africa: extended follow-up of a single-centre, open-label, non-inferiority, randomised controlled trial.

BACKGROUND: Reduced-dosing pneumococcal conjugate vaccine (PCV) schedules (single primary dose plus booster [1+1]) are being considered and have been deployed in the UK. We aimed to evaluate the persistence of serotype-specific immunity until age 5 years in infants randomly assigned to 1+1 or two primary doses plus booster (2+1) schedules of 10-valent (PCV10) or 13-valent (PCV13) vaccine. METHODS: In the original, single-centre, open-label, non-inferiority, randomised controlled trial, infants not exposed to HIV were randomly assigned (1:1:1:1:1:1) using block randomisation into the six following groups: single-dose PCV10 or PCV13 at 6 weeks (6w+1) or 14 weeks (14w+1), or two doses of PCV10 or PCV13 at 6 weeks and 14 weeks (2+1), with all receiving a 9-month booster. In this extended follow-up, serotype-specific serum IgG geometric mean concentrations (GMCs) were measured by in-house Luminex assay at age 3 years, 4 years, and 5 years. Non-inferiority was defined as the lower-bound of the 95% CI of the GMC ratio exceeding 0·5 for at least ten of the PCV13 serotypes and at least eight of the PCV10 serotypes. This follow-up study is registered at ClinicalTrials.gov (NCT04275284). FINDINGS: In the original trial, of the 1695 who were screened, 600 children were enrolled and randomly assigned to six study groups (100 in each group) from Jan 9 to Sept 20, 2017. Of these, 354 (59%) were included in the follow-up study, including 54 from 6w+1 PCV10, 56 from 14w+1 PCV10, 64 from 2+1 PCV10, 60 from 6w+1 PCV13, 57 from 14w+1 PCV13, and 63 from the 2+1 PCV13 study groups. 986 blood samples were collected across three annual visits (349 at 3 years, 334 at 4 years, and 303 at 5 years) between Feb 18, 2020 and Aug 24, 2022. Both PCV13 1+1 schedules remained non-inferior to the PCV13 2+1 schedule up until age 5 years. Both PCV10 1+1 schedules met non-inferiority at 3 years but did not meet the non-inferiority criteria at 4 years and 5 years. Comparison of the PCV10 2+1 and PCV13 2+1 schedules demonstrated similar IgG GMCs for the ten shared serotypes up until age 5 years, with PCV13 outperforming PCV10 across most serotypes in 1+1 groups. INTERPRETATION: A reduced PCV13 1+1 schedule, primed at either 6 weeks or 14 weeks, maintained non-inferior serotype-specific GMCs relative to the PCV13 2+1 schedule up until age 5 years, supporting schedule transition in countries with well established PCV programmes. The PCV10 1+1 schedules did not meet non-inferiority criteria compared with the PCV10 2+1 schedule by age 4 years. FUNDING: Gates Foundation and South African Medical Research Council.